2a68

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[[Image:2a68.gif|left|200px]]
[[Image:2a68.gif|left|200px]]
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{{Structure
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<!--
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|PDB= 2a68 |SIZE=350|CAPTION= <scene name='initialview01'>2a68</scene>, resolution 2.50&Aring;
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The line below this paragraph, containing "STRUCTURE_2a68", creates the "Structure Box" on the page.
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|SITE=
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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|LIGAND= <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=RBT:RIFABUTIN'>RBT</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene>
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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|ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/DNA-directed_RNA_polymerase DNA-directed RNA polymerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.6 2.7.7.6] </span>
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or leave the SCENE parameter empty for the default display.
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|GENE=
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|DOMAIN=
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{{STRUCTURE_2a68| PDB=2a68 | SCENE= }}
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|RELATEDENTRY=[[1iw7|1IW7]], [[1smy|1SMY]]
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2a68 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2a68 OCA], [http://www.ebi.ac.uk/pdbsum/2a68 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2a68 RCSB]</span>
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}}
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'''Crystal structure of the T. thermophilus RNA polymerase holoenzyme in complex with antibiotic rifabutin'''
'''Crystal structure of the T. thermophilus RNA polymerase holoenzyme in complex with antibiotic rifabutin'''
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[[Category: Vassylyeva, M N.]]
[[Category: Vassylyeva, M N.]]
[[Category: Wakatsuki, S.]]
[[Category: Wakatsuki, S.]]
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[[Category: antibiotic]]
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[[Category: Antibiotic]]
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[[Category: rifabutin]]
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[[Category: Rifabutin]]
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[[Category: riken structural genomics/proteomics initiative]]
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[[Category: Riken structural genomics/proteomics initiative]]
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[[Category: rna polymerase holoenzyme]]
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[[Category: Rna polymerase holoenzyme]]
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[[Category: rsgi]]
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[[Category: Rsgi]]
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[[Category: structural genomic]]
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[[Category: Structural genomic]]
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[[Category: transcription regulation]]
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[[Category: Transcription regulation]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 18:39:35 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 01:48:22 2008''
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Revision as of 15:39, 3 May 2008

Image:2a68.gif

Template:STRUCTURE 2a68

Crystal structure of the T. thermophilus RNA polymerase holoenzyme in complex with antibiotic rifabutin


Overview

Rifamycins, the clinically important antibiotics, target bacterial RNA polymerase (RNAP). A proposed mechanism in which rifamycins sterically block the extension of nascent RNA beyond three nucleotides does not alone explain why certain RNAP mutations confer resistance to some but not other rifamycins. Here we show that unlike rifampicin and rifapentin, and contradictory to the steric model, rifabutin inhibits formation of the first and second phosphodiester bonds. We report 2.5 A resolution structures of rifabutin and rifapentin complexed with the Thermus thermophilus RNAP holoenzyme. The structures reveal functionally important distinct interactions of antibiotics with the initiation sigma factor. Strikingly, both complexes lack the catalytic Mg2+ ion observed in the apo-holoenzyme, whereas an increase in Mg2+ concentration confers resistance to rifamycins. We propose that a rifamycin-induced signal is transmitted over approximately 19 A to the RNAP active site to slow down catalysis. Based on structural predictions, we designed enzyme substitutions that apparently interrupt this allosteric signal.

About this Structure

2A68 is a Protein complex structure of sequences from Thermus thermophilus. Full crystallographic information is available from OCA.

Reference

Allosteric modulation of the RNA polymerase catalytic reaction is an essential component of transcription control by rifamycins., Artsimovitch I, Vassylyeva MN, Svetlov D, Svetlov V, Perederina A, Igarashi N, Matsugaki N, Wakatsuki S, Tahirov TH, Vassylyev DG, Cell. 2005 Aug 12;122(3):351-63. PMID:16096056 Page seeded by OCA on Sat May 3 18:39:35 2008

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